There is a need in the art for novel therapeutic agents to treat cancer. Heat shock protein-90 (Hsp90) supports tumorigenesis. Nonetheless, there is a paucity of evidence demonstrating whether intracellular or secreted form of Hsp90 plays a primary role and should be therapeutically targeted. Herein, the inventors demonstrate that the secreted, but not intracellular, Hsp90α is responsible for tumor cell's ability to migrate and invade. Knockout of Hsp90α in MDA-MB-231 cells specifically abolishes the tumor cells' intrinsic motility and invasiveness. These defects are fully rescued by addition of recombinant Hsp90α, but not Hsp90β, protein to Hsp90α-knockout cells. Monoclonal antibodies described herein, 1G6-D7 and 5C4-D, targeting the F-5 epitope of tumor cell-secreted Hsp90α block tumor cell migration and invasion. The inventors determined that Lys-270 and Lys-277 in Hsp90α determine the unique function of secreted Hsp90α and are sufficient to convert Hsp90β to a Hsp90α-like molecule to rescue motility and invasion defects in Hsp90α-knockout cells. Thus provided herein are new targets (for example, the dual lysine region of tumor-secreted Hsp90α) and new therapeutic antibodies (IG6-D7 and 5C4-D) that target Hsp90α.